title: Inactivated West Nile Virus (WNV) vaccine, Duvaxyn WNV, protects against a highly neuroinvasive lineage 2 WNV strain in mice.
abstract: BACKGROUND
  Lineage 2 West Nile Virus (WNV) is endemic to southern Africa and Madagascar, and has recently been associated with encephalitis outbreaks in humans and horses in South Africa, central Europe, Italy and Greece. Commercial vaccines have mostly been evaluated against WNV lineage 1 strains and their efficacy against lineage 2 strains rarely reported.
  
  
  METHODS
  To evaluate protection of Duvaxyn WNV vaccine against lineage 2 strains associated with encephalitis in South Africa, mice were vaccinated twice intramuscularly three weeks apart, and challenged four weeks later with highly neuroinvasive lineage 1 strain NY385/99 or lineage 2 strain SPU93/01. Neutralising antibody titres were measured at the time of challenge and three weeks later. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were conducted on brains of mice that succumbed during the trial, on controls and on vaccinated mice that survived.
  
  
  RESULTS
  Serum neutralising antibodies in vaccinated mice were detected but low three weeks after primovaccination. Three weeks post-challenge, vaccinated mice had significantly higher serum neutralising antibody titres against both lineages than unvaccinated controls. After challenge, all vaccinated mice remained healthy but all unvaccinated mice demonstrated severe neurological signs with 75% mortality rate. WNV was not detected in brains of vaccinated mice whereas virus replicated in most unvaccinated mice challenged with either lineage. Gross and microscopic lesions were found only in unvaccinated mice challenged with both lineages.
  
  
  CONCLUSIONS
  Duvaxyn WNV vaccine provided complete protection against challenge with lineage 2 WNV and stimulated significant cross protective neutralising antibodies in mice against lineage 2.
authors.affiliation: Zoonosis Research Unit, Department Medical Virology, Room 2.72, Pathology Building, Prinshof Campus, 5 Bophela Road, University of Pretoria, South Africa. marietjie.venter@up.ac.za
authors.forename: Marietjie
authors.initials: M
authors.lastname: Venter
authors.forename: Petrus Janse
authors.initials: PJ
authors.lastname: van Vuren
authors.forename: Juliet
authors.initials: J
authors.lastname: Mentoor
authors.forename: Janusz
authors.initials: J
authors.lastname: Paweska
authors.forename: June
authors.initials: J
authors.lastname: Williams
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D001921:Brain / Q000276:immunology / Q000821:virology; D003429:Cross Reactions; D006736:Horses / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000032:analysis; D015164:Vaccines, Inactivated / Q000276:immunology / Q000494:pharmacology*; D014901:West Nile Fever / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D053060:West Nile Virus Vaccines / Q000276:immunology / Q000494:pharmacology*; D014902:West Nile virus / Q000472:pathogenicity*
chemical_list: D057134:Antibodies, Neutralizing; D012367:RNA, Viral; D015164:Vaccines, Inactivated; D053060:West Nile Virus Vaccines
keywords: Cross protection; Duvaxyn WNV vaccine; Horses; Inactivated vaccine; Lineage 1; Lineage 2; Neutralising antibodies; West Nile Virus